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NMDA receptors are expressed by small-cell lung cancer and are potential targets for effective treatment
We previously showed that functional N-methyl-D-aspartate (NMDA) receptors are expressed by human neuroblastoma cells. In this study we demonstrate functional NMDAR1 and NMDAR2 receptors are expressed by small-cell lung cancer (SCLC) classical cell lines NCI H146, NCI H345, and DMS 53, by variant ce...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262385/ https://www.ncbi.nlm.nih.gov/pubmed/22291485 |
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author | North, William G Gao, Guohong Jensen, Amy Memoli, Vincent A Du, Jinlin |
author_facet | North, William G Gao, Guohong Jensen, Amy Memoli, Vincent A Du, Jinlin |
author_sort | North, William G |
collection | PubMed |
description | We previously showed that functional N-methyl-D-aspartate (NMDA) receptors are expressed by human neuroblastoma cells. In this study we demonstrate functional NMDAR1 and NMDAR2 receptors are expressed by small-cell lung cancer (SCLC) classical cell lines NCI H146, NCI H345, and DMS 53, by variant cell line NCI H82, and by most SCLC tumors, and that these receptors are important for the growth of human SCLC tumor xenografts in mice. Reverse transcription-polymerase chain reaction demonstrated mRNA for both receptors, with sequences identical to those for human mRNAs, are expressed in all four cell lines, and these generated proteins of the expected sizes 120 and 170 kDa. Cell viability tests showed cell growth was significantly (P < 0.0001) impaired by NMDAR1 antagonists MK-801 and memantine. Ifenprodil and Ro25-6981, NMDAR2B antagonists at the polyamine site, also significantly (P < 0.001) inhibited the growth/survival of these cells. Alternatively, the glycine-binding antagonist, L701, 324, increased viability to 140% and 120% in NCI H345 and NCI H82 cells after 48 hours of incubation. Immunohistochemistry of SCLC tumors with our polyclonal antibodies gave specific positive staining for the NMDAR1 receptor in 8 of 10 tissues examined. Small amounts of these same antibodies significantly reduced the growth of NCI-H345 cells up to 25% (P < 0.001). When NCI H345 cells were grown as tumor xenografts in mice, the growth of these tumors was reduced by 60% (P < 0.001) by treatments with MK-801 over five days. All of these data point to active NMDAR receptors possibly having an important influence on SCLC growth and survival. |
format | Online Article Text |
id | pubmed-3262385 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-32623852012-01-30 NMDA receptors are expressed by small-cell lung cancer and are potential targets for effective treatment North, William G Gao, Guohong Jensen, Amy Memoli, Vincent A Du, Jinlin Clin Pharmacol Original Research We previously showed that functional N-methyl-D-aspartate (NMDA) receptors are expressed by human neuroblastoma cells. In this study we demonstrate functional NMDAR1 and NMDAR2 receptors are expressed by small-cell lung cancer (SCLC) classical cell lines NCI H146, NCI H345, and DMS 53, by variant cell line NCI H82, and by most SCLC tumors, and that these receptors are important for the growth of human SCLC tumor xenografts in mice. Reverse transcription-polymerase chain reaction demonstrated mRNA for both receptors, with sequences identical to those for human mRNAs, are expressed in all four cell lines, and these generated proteins of the expected sizes 120 and 170 kDa. Cell viability tests showed cell growth was significantly (P < 0.0001) impaired by NMDAR1 antagonists MK-801 and memantine. Ifenprodil and Ro25-6981, NMDAR2B antagonists at the polyamine site, also significantly (P < 0.001) inhibited the growth/survival of these cells. Alternatively, the glycine-binding antagonist, L701, 324, increased viability to 140% and 120% in NCI H345 and NCI H82 cells after 48 hours of incubation. Immunohistochemistry of SCLC tumors with our polyclonal antibodies gave specific positive staining for the NMDAR1 receptor in 8 of 10 tissues examined. Small amounts of these same antibodies significantly reduced the growth of NCI-H345 cells up to 25% (P < 0.001). When NCI H345 cells were grown as tumor xenografts in mice, the growth of these tumors was reduced by 60% (P < 0.001) by treatments with MK-801 over five days. All of these data point to active NMDAR receptors possibly having an important influence on SCLC growth and survival. Dove Medical Press 2010-04-01 /pmc/articles/PMC3262385/ /pubmed/22291485 Text en © 2010 North et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. |
spellingShingle | Original Research North, William G Gao, Guohong Jensen, Amy Memoli, Vincent A Du, Jinlin NMDA receptors are expressed by small-cell lung cancer and are potential targets for effective treatment |
title | NMDA receptors are expressed by small-cell lung cancer and are potential targets for effective treatment |
title_full | NMDA receptors are expressed by small-cell lung cancer and are potential targets for effective treatment |
title_fullStr | NMDA receptors are expressed by small-cell lung cancer and are potential targets for effective treatment |
title_full_unstemmed | NMDA receptors are expressed by small-cell lung cancer and are potential targets for effective treatment |
title_short | NMDA receptors are expressed by small-cell lung cancer and are potential targets for effective treatment |
title_sort | nmda receptors are expressed by small-cell lung cancer and are potential targets for effective treatment |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262385/ https://www.ncbi.nlm.nih.gov/pubmed/22291485 |
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